| Title: |
Nusinersen versus sham control in infantile-onset spinal muscular atrophy |
| Authors: |
Finkel, RS; Mercuri, E; Darras, BT; Connolly, AM; Kuntz, NL; Kirschner, J; Chiriboga, CA; Saito, K; Servais, L; Tizzano, E; Topaloglu, H; Tulinius, M; Montes, J; Glanzman, AM; Bishop, K; Zhong, ZJ; Gheuens, S; Bennett, CF; Schneider, E; Farwell, W; De Vivo, DC; Bradley, WG; Schroth, MK; Bodensteriner, JB; Davis, CS; Shell, R; Hen, J; Austin, ED; Aziz-Zaman, S; Cappell, J; Constantinescu, A; Cruz, R; Dastgir, J; Dunaway, S; Engelstad, K; Gormley, M; Holuba La Marca, N; Khandji, A; Kramer, S; Marra, J; Ortiz-Miller, C; Popolizio, M; Salazar, R; Sanabria, L; Weimer, L; Anand, P; Gadeken, R; Golumbek, PT; Siener, C; Zaidman, CM; Al-Ghamdi, F; Berde, C; Ghosh, P; Graham, R; Harrington, T; Koka, A; Laine, R; Liew, W; Mirek, E; Ordonez, G; Pasternak, A; Quigley, J; Sethna, N; Souris, M; Szelag, H; Wand, L; Day, JW; D'Souza, G; Duong, TT; Gee, R; Kitsuwa-Lowe, J; McFall, D; Patnaik, S; Paulose, S; Perez, J; Proud, C; Purse, B; Ramamurthi, RJ; Sakamuri, S; Sampson, J; Sanjanwala, B; Tesi Rocha, AC; Watson, K; Welsh, L; Pena, LDM; Case, L; Coates, J; DeArmey, S; Homi, MM; Milleson, C; Nelson, N; Ross, A; Smith, E; Taicher, B; Wootton, J; Finanger, E; Benjamin, D; Frank, A; Roberts, C; Russman, B; Farrar, Michelle ; https://orcid.org/0000-0002-4472-0902; Kandula, Tejaswi ; https://orcid.org/0000-0002-4355-4965 |
| Source: |
urn:ISSN:0028-4793; urn:ISSN:1533-4406; New England Journal of Medicine, 377, 18, 1723-1732 |
| Publisher Information: |
Massachusetts Medical Society 2017-11-02 |
| Document Type: |
Electronic Resource |
| Abstract: |
BACKGROUND: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODS: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTS: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P |
| Index Terms: |
3213 Paediatrics; 32 Biomedical and Clinical Sciences; Clinical Research; Orphan Drug; Spinal Muscular Atrophy; Pediatric Research Initiative; Neurosciences; Genetics; Rare Diseases; Clinical Trials and Supportive Activities; Neurodegenerative; Patient Safety; 3 Good Health and Well Being; Age of Onset; Disease-Free Survival; Double-Blind Method; Female; Humans; Infant; Injections, Spinal; Male; Motor Skills; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Respiration, Artificial; Spinal Muscular Atrophies of Childhood; Survival Analysis; Survival of Motor Neuron 2 Protein; ENDEAR Study Group; anzsrc-for: 3213 Paediatrics; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 111403 Paediatrics; anzsrc-for: 110904 Neurology and Neuromuscular Diseases; anzsrc-for: 11 Medical and Health Sciences; anzsrc-for: 42 Health sciences; journal article; http://purl.org/coar/resource_type/c_6501 |
| URL: |
http://hdl.handle.net/1959.4/unsworks_49227; https://unsworks.unsw.edu.au/bitstreams/8464c3c3-9df7-43a0-be50-b5125661ad27/download; https://doi.org/10.1056/NEJMoa1702752 |
| Availability: |
Open access content. Open access content; open access; https://purl.org/coar/access_right/c_abf2; CC-BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0; free_to_read |
| Note: |
application/pdf |
| Other Numbers: |
LJ1 oai:unsworks.library.unsw.edu.au:1959.4/unsworks_49227; 1031076708 |
| Contributing Source: |
UNIV OF NEW S WALES; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1031076708 |
| Database: |
OAIster |